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利用计算机模拟方法鉴定类鼻疽伯克霍尔德菌免疫原性蛋白的CD4+ T细胞表位并研究HLA分布——类鼻疽病疫苗开发的关键策略

Identification of CD4+ T-cell epitope and investigation of HLA distribution for the immunogenic proteins of Burkholderia pseudomallei using in silico approaches - A key vaccine development strategy for melioidosis.

作者信息

Swetha Rayapadi G, Sandhya Madangopal, Ramaiah Sudha, Anbarasu Anand

机构信息

Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India.

Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India.

出版信息

J Theor Biol. 2016 Jul 7;400:11-8. doi: 10.1016/j.jtbi.2016.04.009. Epub 2016 Apr 13.

DOI:10.1016/j.jtbi.2016.04.009
PMID:27086038
Abstract

Melioidosis is a serious infectious diseases affecting multi-organ system in humans with high mortality rate. The disease is caused by the bacterium, Burkholderia pseudomallei and it is intrinsically resistant to many antibiotics. Thus, there is an urgent need for protective vaccine against B. pseudomallei; which may reduce morbidity and mortality in endemic areas. The identification of peptides that bind to major histocompatibility complex II class helps in understanding the nature of immune response and identifying T-cell epitopes for the design of new vaccines. Previous studies indicate that, ompA, bipB, fliC and groEL proteins of B. pseudomallei stimulate CD4+ T-cell immune response and act as protective immunogens. However, the data for CD4+ T-cell epitopes of these immunogenic proteins are very limited. Hence, in this present study we attempted to identify CD4+ T-cell epitopes in B. pseudomallei immunogenic proteins using in silico approaches. We did population coverage analysis for these identified epitopic core sequences to identify individuals in endemic areas expected to respond to a given set of these epitopes on the basis of HLA genotype frequencies. We observed that eight epitopic core sequences, two from each immunogenic protein, were associated with the maximum number of HLA-DR binding alleles. These eight peptides are found to be immunogenic in more than 90% of population in endemic areas considered. Thus, these eight peptides containing epitopic core sequences may act as probable vaccine candidates and they may be considered for the development of epitope-based vaccines for melioidosis.

摘要

类鼻疽是一种严重的传染病,可影响人类的多器官系统,死亡率很高。该疾病由类鼻疽伯克霍尔德菌引起,它对许多抗生素具有内在抗性。因此,迫切需要针对类鼻疽伯克霍尔德菌的保护性疫苗;这可能会降低流行地区的发病率和死亡率。鉴定与主要组织相容性复合体II类结合的肽有助于了解免疫反应的性质,并鉴定用于设计新疫苗的T细胞表位。先前的研究表明,类鼻疽伯克霍尔德菌的ompA、bipB、fliC和groEL蛋白可刺激CD4+T细胞免疫反应,并作为保护性免疫原。然而,这些免疫原性蛋白的CD4+T细胞表位数据非常有限。因此,在本研究中,我们试图使用计算机方法鉴定类鼻疽伯克霍尔德菌免疫原性蛋白中的CD4+T细胞表位。我们对这些鉴定出的表位核心序列进行了群体覆盖率分析,以根据HLA基因型频率确定流行地区中预期对给定的一组这些表位有反应的个体。我们观察到八个表位核心序列,每个免疫原性蛋白各有两个,与最大数量的HLA-DR结合等位基因相关。在所考虑的流行地区,发现这八种肽在90%以上的人群中具有免疫原性。因此,这些含有表位核心序列的八种肽可能作为潜在的疫苗候选物,可考虑用于开发基于表位的类鼻疽疫苗。

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